Clinical trial · Observational
Ceftazidime-Avibactam PK/PD and Resistance in Hematology Patients
Prospective Exploratory Study of Standard-Dose Ceftazidime-Avibactam PK/PD Target Attainment, Clinical Outcomes, and Induced Resistance in Patients With Hematological Malignancies
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is a prospective, single-arm, observational, exploratory clinical study to evaluate whether the standard fixed dose of ceftazidime-avibactam (CAZ-AVI) achieves sufficient drug exposure (pharmacokinetic/pharmacodynamic, or PK/PD targets) in patients with blood cancers (or those undergoing stem cell transplantation). Patients with hematological malignancies are at high risk for severe, drug-resistant Gram-negative bacterial infections due to weakened immune systems. CAZ-AVI is a critical antibiotic used to treat these infections. However, there is limited evidence on whether the standard recommended dose achieves adequate drug concentrations for both ceftazidime and avibactam simultaneously in this specific patient group, and whether low drug exposure drives the development of antibiotic resistance during treatment. This study will enroll 60 participants who are already prescribed CAZ-AVI by their treating physicians based on routine clinical needs. The study will not change or interfere with any clinical treatment decisions. To measure drug levels, 5 small blood samples (about 2-3 mL each) will be collected within one dosing interval after the drug reaches a steady level in the body (typically 48 to 72 hours after starting treatment). Microbiological samples (such as blood cultures or swabs) will also be collected at multiple time points to monitor bacterial clearance and detect any newly developed resistance. Participants will be followed up for clinical outcomes and survival status up to 30 days after the completion of treatment. The primary goal of this study is to determine the percentage of patients who achieve the target drug exposure for both ceftazidime and avibactam simultaneously. The secondary goals are to observe clinical cure rates, bacterial clearance rates, 30-day survival, and the rate of newly induced antibiotic resistance during therapy.
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Drug Resistance, Bacterial | — | UNRESOLVED | — |
| Gram-Negative Bacterial Infections | — | UNRESOLVED | — |
| Hematologic Neoplasms | Hematopoietic and Lymphoid Cell Neoplasm | ALIAS | 0.90 |
| Klebsiella Pneumoniae Infections | — | UNRESOLVED | — |
| Pseudomonas Aeruginosa Infection | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Ceftazidime-avibactam | Drug | — | UNRESOLVED |
| Therapeutic Drug Monitoring (TDM) and Microbiological Surveillance | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- CAZ-AVI Single-Arm Observation Group
- description
- Patients with hematological malignancies or those undergoing hematopoietic stem cell transplantation (HSCT) who are prescribed standard-dose ceftazidime-avibactam (CAZ-AVI) for suspected or confirmed Gram-negative bacterial infections based solely on routine clinical decisions \[4, 6.1, 17\]. This group will undergo standard-of-care antibiotic therapy combined with protocol-specified therapeutic drug monitoring (TDM) and microbiological surveillance.
- interventionNames
- Drug: Ceftazidime-avibactam
- Procedure: Therapeutic Drug Monitoring (TDM) and Microbiological Surveillance
Primary outcomes (1)
- measure
- Joint Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Rate of Ceftazidime-Avibactam
- timeFrame
- 48 to 72 hours after starting ceftazidime-avibactam therapy (assessed over a single dosing interval at steady state, typically after the 4th or 5th dose).
- description
- The percentage of patients who simultaneously achieve the target drug exposure for both ceftazidime and avibactam in plasma during the early phase of therapy. The joint PK/PD target attainment is defined as meeting both of the following criteria concurrently within a single dosing interval: 1. Ceftazidime free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the pathogen for at least 50% of the dosing interval (50% fT \> MIC). 2. Avibactam free drug concentration remains above 1 mg/L for at least 50% of the dosing interval (50% fT \> 1 mg/L). The pathogen's MIC is determined under a fixed concentration of 4 mg/L avibactam using the broth microdilution (BMD) method.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 16 Years
Show eligibility criteria text
Inclusion Criteria: * Age 16 years or older. * Diagnosed with hematological malignancies (including but not limited to acute leukemia, lymphoma, multiple myeloma, or myelodysplastic syndrome \[MDS\]) or having received/undergoing autologous or allogeneic hematopoietic stem cell transplantation (HSCT). * Prescribed ceftazidime-avibactam (CAZ-AVI) therapy for suspected or confirmed Gram-negative bacterial infections based solely on routine clinical decisions. * Expected duration of CAZ-AVI therapy is no less than 72 hours. * Willing and able to comply with the study-specified therapeutic drug monitoring (TDM) and microbiological surveillance. Exclusion Criteria: * Known severe allergy or hypersensitivity to ceftazidime, avibactam, cephalosporins, or other beta-lactam antibiotics. * Confirmed infection caused by metallo-beta-lactamase (MBL)-producing pathogens, without receiving appropriate combination therapy. * Expected survival time of less than 72 hours. * Inability to complete critical pharmacokinetic (TDM) or microbiological sampling. * Pregnancy or lactation. * Any other condition that, in the opinion of the investigator, makes the patient unsuitable for study inclusion.
References
Publications (0)
Data not yet available